An event-related function mapping of higher cortical functions using electrocorticography in epilepsy patients

Abstract

Epilepsy surgery is an effective treatment for some people whose seizure cannot be controlled by medications. When planning for epilepsy surgery, it is important to create a brain map of various cortical functions. Because the surgery resects several cortical areas which are identified as epileptic foci, loss of brain functions may be caused after the surgery. To avoid the loss of cortical function, patients and clinicians need to spend much time to examine cortical functions and its localization. Recently, a non-electrical stimulus based functional mapping method for epilepsy patients have been introduced. Several studies have applied the new mapping method for eloquent cortex and validated the usefulness by comparing the mapping result with surgical outcome. These mapping studies focused only on the eloquent cortex including motor and language functions. However, other higher cortical functions, such as attention or memory functions, also need to be investigated before epilepsy surgery for keeping loss of functions to a minimum. This thesis proposed an event-related experimental design based intraoperative mapping of higher cortical function. Because the event-related experimental designs include many trials repeating the same task, statistical analysis can be used to maximize the differences of brain activities according to the experimental states. Also, the designs which have developed for cognitive studies, such as lesion study or functional magnetic resonance imaging study, can easily be adopted to the event-related design giving possibility for mapping the higher cortical functions. To evaluate the proposed method, at first, the mapping result of eloquent cortex was compared to the result of direct cortical stimulation mapping. The electrodes identified as Wernicke’s area tend to be mapped in the earlier stage of the processing (before speech onset). Activity in tongue motor area or Broca’s area were found near speech onset and the activity lasted until the end of speech. The second work was applying the proposed mapping method to other higher cortical function which is not currently examined during the surgery. In this study, the spatial attention function was investigated by borrowing an experimental task from a previous study conducted by Malhotra. The activities were mapped on the superior parietal cortex where is known to play an important role in spatial cognitive processes. Several electrodes on the frontal cortex and inferior parietal cortex were also mapped indicating the possibility of frontoparietal connection of top-down process of attention. These results suggested that the event-related function mapping method could provide the accurate mapping of the higher cortical functions. Therefore, the result of this study can be great beneficial for the patients who are planning epilepsy surgery. Furthermore, this method may be applied to the studies about the neural bases of cognitive functions. |간질 수술은 약 처방을 통해 간질 발작이 통제되지 않는 경우 행해지는 수술로, 수술을 행함에 있어 여러 가지 고려해야 할 사항이 있다. 그 중에 가장 중요한 것은 대뇌의 기능에 대한 지도를 작성하는 것으로, 수술에 의해 뇌 조직이 제거되는 과정에서 인지기능의 손실을 최소화하기 위해서 수행된다. 기존에는 전기자극을 이용한 방법으로 이러한 뇌 기능 지도를 작성하게 되는데, 이를 위해서 의사와 환자 모두 상당한 시간과 노력을 필요로 한다. 최근에 개발된 기술은 전기자극을 이용하지 않고도 뇌 지도를 작성할 수 있도록 하였는데, 이 방법이 소개 된 후 몇 팀의 연구자들은 새로운 기술을 적용하여 주요기능 피질(eloquent cortex)에 대한 지도를 작성하고, 수술의 예후와 비교하는 연구를 통하여 이 기술의 유용성을 확인하였다. 그럼에도 불구하고, 기존의 모든 연구들은 언어기능과 관련된 주요 기능들에 대해서만 평가가 가능하기 때문에 수술 부위에 포함되는 다른 고위인지기능에 대한 평가가 제외되었고, 이러한 기능들의 손상을 최소화 하기 위해서는 새로운 평가방법의 개발이 필요하다. 본 논문에서는 사건 관련 시험기법을 적용하여 수술 중에 고위인지기능의 뇌 지도를 작성하는 기술(event-related function mapping, ERFM)을 제안한다. 사건 관련 시험기법은 다수의 반복적인 작업을 수행함과 동시에 뇌 신호를 획득하기 때문에 통계적인 분석을 적용하는 데에 유리하고, 따라서 뇌파의 변화를 최대화하여 관찰할 수 있는 장점이 있다. 또한 기존에 인지기능 평가를 위하여 사용되던 시험들 중 다수가 사건 관련 기법과 유사한 블록 디자인으로 되어있기 때문에 쉽게 변형하여 적용이 가능하다. 제시된 기술을 검증하기 위해서 우선 명확한 비교대상이 있는 언어기능을 평가하였다. 언어기능의 경우 전기자극을 통한 뇌 지도 작성을 통해 Wernicke 영역과 Broca 영역을 포함한 운동기능 영역을 확인할 수 있었으며, Wernicke영역의 경우 실제 말하기 이전 구간에서 확연하게 구분이 되었고, Broca 영역과 운동기능 영역의 경우 실제 말하는 구간과 연관되어 구분이 되는 것을 확인하였다. 다음으로는 앞에서 검증된 ERFM 기술을 적용하여 기존에 수행되지 않았던 집중력과 관련된 기능의 지도를 확인하였다. 이 검증에서 사용된 시험은 기존에 인지기능 연구에서 사용되었던 것을 그대로 차용하였으며 집중력 중에서도 위치정보에 대한 집중력을 확인하는 시험이었다. 해당 논문의 연구 결과와 ERFM에 의한 결과는 상당히 유사하였고, 특히 위치 집중력을 가장 잘 나타내는 상부 두정엽(superior parietal lobule)에서의 전극이 확연히 구분되었다. 그 뿐만 아니라, 하부 두정엽(inferior parietal lobule)과 전두엽(frontal lobe) 일부에서도 전극의 활성도가 확인되었는데, 이는 전두엽과 두정엽을 연결하는 하향식(top-down) 집중관련 신호처리 시스템을 나타내는 것으로 추측할 수 있다. 결과적으로 본 연구에서 제시된 ERFM 기법을 통해 고위 인지기능에 대한 지도를 작성할 수 있다는 것을 확인하였으며, 이 기술을 적용함으로써 간질 수술을 하는 환자들에게 있어 인지기능의 손실을 최소화 할 수 있는 가능성을 보였다. 또한 이러한 기술을 적용함으로써 기존 연구방법의 한계 때문에 연구되지 못했던 다양한 고위인지기능에 대한 연구에도 도움이 될 것으로 예상된다.; Epilepsy surgery is an effective treatment for some people whose seizure cannot be controlled by medications. When planning for epilepsy surgery, it is important to create a brain map of various cortical functions. Because the surgery resects several cortical areas which are identified as epileptic foci, loss of brain functions may be caused after the surgery. To avoid the loss of cortical function, patients and clinicians need to spend much time to examine cortical functions and its localization. Recently, a non-electrical stimulus based functional mapping method for epilepsy patients have been introduced. Several studies have applied the new mapping method for eloquent cortex and validated the usefulness by comparing the mapping result with surgical outcome. These mapping studies focused only on the eloquent cortex including motor and language functions. However, other higher cortical functions, such as attention or memory functions, also need to be investigated before epilepsy surgery for keeping loss of functions to a minimum. This thesis proposed an event-related experimental design based intraoperative mapping of higher cortical function. Because the event-related experimental designs include many trials repeating the same task, statistical analysis can be used to maximize the differences of brain activities according to the experimental states. Also, the designs which have developed for cognitive studies, such as lesion study or functional magnetic resonance imaging study, can easily be adopted to the event-related design giving possibility for mapping the higher cortical functions. To evaluate the proposed method, at first, the mapping result of eloquent cortex was compared to the result of direct cortical stimulation mapping. The electrodes identified as Wernicke’s area tend to be mapped in the earlier stage of the processing (before speech onset). Activity in tongue motor area or Broca’s area were found near speech onset and the activity lasted until the end of speech. The second work was applying the proposed mapping method to other higher cortical function which is not currently examined during the surgery. In this study, the spatial attention function was investigated by borrowing an experimental task from a previous study conducted by Malhotra. The activities were mapped on the superior parietal cortex where is known to play an important role in spatial cognitive processes. Several electrodes on the frontal cortex and inferior parietal cortex were also mapped indicating the possibility of frontoparietal connection of top-down process of attention. These results suggested that the event-related function mapping method could provide the accurate mapping of the higher cortical functions. Therefore, the result of this study can be great beneficial for the patients who are planning epilepsy surgery. Furthermore, this method may be applied to the studies about the neural bases of cognitive functions.